Research Summary: An important area of current investigation in our efforts to understand the mechanism of cellular control and development is the nature and operation of protein-nucleic acid interactions. In addition, the packaging of DNA in biological ultrastructure, for example, in bacteriophage and chromosomes is still not well-understood and remains an important problem in molecular biology. Our initial goals are the synthesis of cleavable protein-nucleic acid and nucleic acid-nucleic acid (duplex-duplex) crosslinking reagents. The chemically reactive protein specific and nucleic acid specific moieties are contained within the reagent itself allowing its use in a wide variety of systems. A photochemically activated intercalating agent would be well suited as the nucleic acid specific portion of the crosslinkers. Current research in our group involves the chemical modification of psoralen and ethidium bromide intercalating drugs. Finally, our growing experience in the nucleic acid:drug field suggests many exciting possibilities in the area of the nature of the molecular recognition of DNA by small molecules. We have recently synthesized several new polyintercalating drugs in order to test for high binding constants and sequence specificity similar to those found with repressor proteins.